Development and Prospective Validation of a Heterogeneous Treatment Effect-Based Decision Model for Transarterial Chemoembolization Combined With or Without Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma

Overview

Unresectable hepatocellular carcinoma (uHCC) constitutes a significant health burden in the Asia-Pacific (APAC) region, particularly in China, where it is frequently associated with hepatitis B virus (HBV) infection and diagnosed at advanced stages. Transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage hepatocellular carcinoma (HCC), though its effectiveness diminishes in unresectable HCC (uHCC) with intermediate-to-high tumor burden. The IMbrave150 trial established atezolizumab plus bevacizumab (Atezo+Bev) as a superior alternative to sorafenib, demonstrating significant survival advantages in uHCC. Given the marked heterogeneity of intermediate-stage HCC, TACE may not benefit all patients equally. The TALENTACE study investigated on-demand TACE combined with Atezo+Bev versus TACE alone in treatment-naïve uHCC patients with intermediate-to-high tumor burden across China and Japan. Results revealed a statistically significant and clinically meaningful improvement in the primary endpoint, TACE- progression-free survival (PFS), though overall survival (OS) remained immature at the time of analysis. This situation establishes a critical and unmet need for randomized controlled trials (RCTs) combined with extensive real-world evidence (RWE) to facilitate the assessment of individualized treatment heterogeneity and provide precise treatment recommendations in China and select Asia-Pacific regions.

Interventions

• Device Heterogeneous Treatment Effect-Based Decision Model
  Heterogeneous Treatment Effect-Based Decision Model

Primary outcome measures

• Overall survival [Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 24 months]

Secondary outcome measures (5)

• TACE-PFS [Time frame: From index date to untreatable progression or TACE failure/refractoriness or any cause of death, whichever occurs first, assessed up to 10 months]
• PFS [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months]
• DoR [Time frame: From the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), assessed up to 10 months]
• TTP [Time frame: From index date to unTACE able progression or TACE failure/refractoriness (as defined above), assessed up to 10 months]
• EHS [Time frame: From index date to the first evidence of Extrahepatic Spread, assessed up to 10 months]

Eligibility criteria

Inclusion criteria

• • Aged≥18 years

• Initiated first-line Atezo+Bev.
• Eligible for TACE treatment or received at least one TACE within ±2 months of Atezo+Bev initiation (before Atezo+Bev start, anytime during Atezo+Bev therapy, or after Atezo+Bev discontinuation).
• Clinically or pathologically diagnosed uHCC before or at the initiation of Atezo/Bev.The evidence of being diagnosed as "unresectable" may include but is not limited to below:

"Unresectable" or "advanced" directly documented in the medical records History of extrahepatic metastasis as evidenced clinically or by radiology, histology or cytology OR China Liver Cancer (CNLC) Stage IIIb

• At least one visit record after the initiation of Atezo+Bev
• No prior systemic therapy for HCC, especially immunotherapy
• No prior locoregional therapy to the target lesion(s)
• At least one measurable untreated lesion
• ECOG Performance Status of 0-2

Exclusion criteria

• • Evidence of extrahepatic spread (EHS)

• Participating in interventional clinical trials.
• Being a candidate for curative treatments
• Any condition representing a contraindication to TACE as determined by the investigators
• Active or history of autoimmune disease or immune deficiency
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
• Evidence of bleeding diathesis or significant coagulopathy
• Missing critical baseline or outcome data

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07109336 · ISMIO2501

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗